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Dexmedetomidine to Lessen Intensive Care Unit (ICU) Agitation (DahLIA)

Primary Purpose

Delirium

Status
Completed
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
Dexmedetomidine
Saline placebo
Sponsored by
Austin Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Delirium focused on measuring Delirium, Intensive Care Unit, Dexmedetomidine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients will be eligible for the study if, in the opinion of the treating clinician, they continue to require mechanical ventilation only because their degree of agitation requires such a high dose of sedative medication (midazolam or propofol, the only commonly used specific sedatives in our unit) that extubation is not possible, AND in the opinion of their treating intensivist their agitation is so severe as to make lessening their sedation unsafe.

These criteria will be objectively quantified as follows:

  • they have required either mechanical restraint and/or anti-delirium or sedative medication in the 4 hours prior to seeking consent AND
  • their Confusion Assessment Method for the ICU (CAM-ICU) test is positive for delirium in the 4 hours prior to seeking consent AND
  • their Motor Activity Assessment Scale (MAAS) score is 5 or more in the 4 hours prior to seeking consent, confirming psychomotor agitation AND
  • their SOFA score is less than or equal to 5 in the 4 hours prior to seeking consent, predicting a mortality or around 5%.

Exclusion Criteria:

  • Age less than 18 years old
  • Pregnancy or breastfeeding
  • Advanced dementia (in the premorbid state requiring professional nursing care)
  • Open or closed head injury
  • Death is deemed imminent and inevitable
  • The patient has previously been enrolled in the DahLIA study

  • Patients who could not be extubated, or who would be intubated within the following 48 hours, even if delirium or agitation were corrected. This will include:

    • Patients receiving high dose opioid for analgesia (not sedation) ( > 40 mg/morphine/day)
    • Patients shortly to return to the operating theatre
    • Patients undergoing repeated invasive procedures, in whom it is desirable to maintain deep sedation
    • Patients likely to require ongoing airway protection or control, or ventilatory support (for example, spinal patients with an inadequate vital capacity)
  • Known allergy to haloperidol or alpha 2 agonists

Sites / Locations

  • Royal North Shore Hospital
  • Toowoomba Hospital
  • Northern Hospital
  • The Western Hospital
  • Austin Hospital
  • The Alfred Hospital
  • Royal Perth Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Dexmedetomidine

Saline placebo

Arm Description

Dexmedetomidine will be administered intravenously as a maintenance infusion of 0.2 to 1.5 mcg/kg/hour, commencing at 0.5 mcg/kg/hour and titrated according to effect, for as long as deemed necessary by the treating physician. Specifically, the study medication may be (as recommended by the manufacturer) continued after extubation, and if discontinued may be restarted at any time up until ICU discharge. The clinician will have the option of using a loading dose of 1.0 mcg/kg IV over 20 minutes, as recommended by the manufacturer. Bedside nursing staff will adjust drug infusion rates as necessary, in consultation with the treating physician, aiming to achieve a Riker Sedation-Agitation Scale 20 score of 4.

An identical syringe to that in the intervention arm, but which does not contain dexmedetomidine, will be provided. The initial rate of infusion and subsequent adjustments will be the same as in the dexmedetomidine group.

Outcomes

Primary Outcome Measures

Ventilator-free hours
The primary outcome measure for the study will be the number of ventilator-free hours in the incident ICU admission in the 7 days following commencement of trial medication, in patients randomised to receive dexmedetomidine or normal saline placebo while receiving all other aspects of standard care.

Secondary Outcome Measures

Time to ICU discharge
Overall ICU length of stay
Time to first extubation
Time taken to achieve a satisfactory sedation score
Time taken to achieve RASS score -2 to +1 and RIKER score 3 or 4
%ICU time spent with a satisfactory sedation score
%ICU time spent with RASS -2 to +1 and RIKER 3 or 4
%ICU time spent with a satisfactory delirium score
% time spent with a negative CAM-ICU assessment
Time taken to achieve a satisfactory agitation score
Time taken to achieve a MAAS score 2-4
%ICU time spent with a satisfactory agitation score
%ICU time spent with a MAAS score 2-4
Need for supplementary sedative medication
total infusion time, mean hourly dose and total dose of propofol, morphine and midazolam.
Need for mechanical restraint
Time to first not requiring restraint and % ICU time spent without mechanical restraint in the 7 days following commencement of trial medication
Need for supplementary antipsychotic medication
Number of doses and total mg delivered of haloperidol, olanzapine, quetiapine, or other anti-psychotic medication as prescribed by the treating physician
Need for tracheostomy
Tracheostomy deemed to be necessary by the treating physician, and actually performed.
Acute hospital length of stay
Total duration of admission to the acute hospital, prior to discharge to home or a skilled or unskilled nursing facility.
Discharge destination
Discharge to home, a skilled nursing facility, residential care, a physical rehabilitation facility, or death.
Daily SOFA score
Daily SOFA score with recording of the component parts
ICU mortality
ICU mortality
Hospital mortality
Death in the acute care hospital
Duration and rate of vasopressor support
total infusion time, and mean hourly dose of noradrenaline and any other inotrope or vasopressor
Need for insertion of a new central venous catheter to facilitate vasopressor / inotropic support
Requirement for reintubation
Reintubation of the trachea to facilitate airway protection or mechanical ventilation, as indicated in the opinion of the treating physician

Full Information

First Posted
June 18, 2010
Last Updated
January 18, 2015
Sponsor
Austin Health
Collaborators
Hospira, now a wholly owned subsidiary of Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT01151865
Brief Title
Dexmedetomidine to Lessen Intensive Care Unit (ICU) Agitation
Acronym
DahLIA
Official Title
A Randomised, Double-blind, Multi-centre Placebo Controlled Trial of Dexmedetomidine for Patients With Agitation and Delirium in the Intensive Care Unit
Study Type
Interventional

2. Study Status

Record Verification Date
January 2015
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Austin Health
Collaborators
Hospira, now a wholly owned subsidiary of Pfizer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary aim of the DahLIA trial is to determine, in patients with ICU-associated delirium and agitation who are otherwise pathophysiologically stable (as defined), the number of ventilator-free hours in the incident ICU admission in the 7 days following commencement of trial medication, in patients randomised to receive dexmedetomidine or placebo while receiving all other aspects of standard care. The null hypothesis assumes no difference in the median number of ventilator-free hours in this ICU admission in the following 7 days, between patients receiving dexmedetomidine and placebo for ICU-associated agitation and delirium.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Delirium
Keywords
Delirium, Intensive Care Unit, Dexmedetomidine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
96 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dexmedetomidine
Arm Type
Active Comparator
Arm Description
Dexmedetomidine will be administered intravenously as a maintenance infusion of 0.2 to 1.5 mcg/kg/hour, commencing at 0.5 mcg/kg/hour and titrated according to effect, for as long as deemed necessary by the treating physician. Specifically, the study medication may be (as recommended by the manufacturer) continued after extubation, and if discontinued may be restarted at any time up until ICU discharge. The clinician will have the option of using a loading dose of 1.0 mcg/kg IV over 20 minutes, as recommended by the manufacturer. Bedside nursing staff will adjust drug infusion rates as necessary, in consultation with the treating physician, aiming to achieve a Riker Sedation-Agitation Scale 20 score of 4.
Arm Title
Saline placebo
Arm Type
Placebo Comparator
Arm Description
An identical syringe to that in the intervention arm, but which does not contain dexmedetomidine, will be provided. The initial rate of infusion and subsequent adjustments will be the same as in the dexmedetomidine group.
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine
Other Intervention Name(s)
Precedex
Intervention Description
Dexmedetomidine will be administered intravenously as a maintenance infusion of 0.2 to 1.5 mcg/kg/hour, commencing at 0.5 mcg/kg/hour and titrated according to effect, for as long as deemed necessary by the treating physician. Specifically, the study medication may be (as recommended by the manufacturer) continued after extubation, and if discontinued may be restarted at any time up until ICU discharge. The clinician will have the option of using a loading dose of 1.0 mcg/kg IV over 20 minutes, as recommended by the manufacturer. Bedside nursing staff will adjust drug infusion rates as necessary, in consultation with the treating physician, aiming to achieve a Riker Sedation-Agitation Scale 20 score of 4.
Intervention Type
Drug
Intervention Name(s)
Saline placebo
Intervention Description
An identical syringe containing only saline with no dexmedetomidine added will be supplied. Initial rate of infusion and subsequent adjustments will be the same as in the active comparator group.
Primary Outcome Measure Information:
Title
Ventilator-free hours
Description
The primary outcome measure for the study will be the number of ventilator-free hours in the incident ICU admission in the 7 days following commencement of trial medication, in patients randomised to receive dexmedetomidine or normal saline placebo while receiving all other aspects of standard care.
Time Frame
7 days following randomisation
Secondary Outcome Measure Information:
Title
Time to ICU discharge
Time Frame
On hospital discharge, or 6 months (whichever is sooner)
Title
Overall ICU length of stay
Time Frame
On hospital discharge, or 6 months (whichever is sooner)
Title
Time to first extubation
Time Frame
On hospital discharge, or 6 months (whichever is sooner)
Title
Time taken to achieve a satisfactory sedation score
Description
Time taken to achieve RASS score -2 to +1 and RIKER score 3 or 4
Time Frame
7 days following randomisation
Title
%ICU time spent with a satisfactory sedation score
Description
%ICU time spent with RASS -2 to +1 and RIKER 3 or 4
Time Frame
7 days following randomisation
Title
%ICU time spent with a satisfactory delirium score
Description
% time spent with a negative CAM-ICU assessment
Time Frame
7 days following randomisation
Title
Time taken to achieve a satisfactory agitation score
Description
Time taken to achieve a MAAS score 2-4
Time Frame
7 days following randomisation
Title
%ICU time spent with a satisfactory agitation score
Description
%ICU time spent with a MAAS score 2-4
Time Frame
7 days following randomisation
Title
Need for supplementary sedative medication
Description
total infusion time, mean hourly dose and total dose of propofol, morphine and midazolam.
Time Frame
7 days following randomisation
Title
Need for mechanical restraint
Description
Time to first not requiring restraint and % ICU time spent without mechanical restraint in the 7 days following commencement of trial medication
Time Frame
7 days following randomisation
Title
Need for supplementary antipsychotic medication
Description
Number of doses and total mg delivered of haloperidol, olanzapine, quetiapine, or other anti-psychotic medication as prescribed by the treating physician
Time Frame
7 days following randomisation
Title
Need for tracheostomy
Description
Tracheostomy deemed to be necessary by the treating physician, and actually performed.
Time Frame
On hospital discharge, or 6 months (whichever is sooner)
Title
Acute hospital length of stay
Description
Total duration of admission to the acute hospital, prior to discharge to home or a skilled or unskilled nursing facility.
Time Frame
On hospital discharge, or 6 months (whichever is sooner)
Title
Discharge destination
Description
Discharge to home, a skilled nursing facility, residential care, a physical rehabilitation facility, or death.
Time Frame
On hospital discharge, or 6 months (whichever is sooner)
Title
Daily SOFA score
Description
Daily SOFA score with recording of the component parts
Time Frame
7 days following randomisation
Title
ICU mortality
Description
ICU mortality
Time Frame
On hospital discharge, or 6 months (whichever is sooner)
Title
Hospital mortality
Description
Death in the acute care hospital
Time Frame
On hospital discharge, or 6 months (whichever is sooner)
Title
Duration and rate of vasopressor support
Description
total infusion time, and mean hourly dose of noradrenaline and any other inotrope or vasopressor
Time Frame
7 days following randomisation
Title
Need for insertion of a new central venous catheter to facilitate vasopressor / inotropic support
Time Frame
7 days following randomisation
Title
Requirement for reintubation
Description
Reintubation of the trachea to facilitate airway protection or mechanical ventilation, as indicated in the opinion of the treating physician
Time Frame
On hospital discharge, or 6 months (whichever is sooner)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients will be eligible for the study if, in the opinion of the treating clinician, they continue to require mechanical ventilation only because their degree of agitation requires such a high dose of sedative medication (midazolam or propofol, the only commonly used specific sedatives in our unit) that extubation is not possible, AND in the opinion of their treating intensivist their agitation is so severe as to make lessening their sedation unsafe. These criteria will be objectively quantified as follows: they have required either mechanical restraint and/or anti-delirium or sedative medication in the 4 hours prior to seeking consent AND their Confusion Assessment Method for the ICU (CAM-ICU) test is positive for delirium in the 4 hours prior to seeking consent AND their Motor Activity Assessment Scale (MAAS) score is 5 or more in the 4 hours prior to seeking consent, confirming psychomotor agitation AND their SOFA score is less than or equal to 5 in the 4 hours prior to seeking consent, predicting a mortality or around 5%. Exclusion Criteria: Age less than 18 years old Pregnancy or breastfeeding Advanced dementia (in the premorbid state requiring professional nursing care) Open or closed head injury Death is deemed imminent and inevitable The patient has previously been enrolled in the DahLIA study Patients who could not be extubated, or who would be intubated within the following 48 hours, even if delirium or agitation were corrected. This will include: Patients receiving high dose opioid for analgesia (not sedation) ( > 40 mg/morphine/day) Patients shortly to return to the operating theatre Patients undergoing repeated invasive procedures, in whom it is desirable to maintain deep sedation Patients likely to require ongoing airway protection or control, or ventilatory support (for example, spinal patients with an inadequate vital capacity) Known allergy to haloperidol or alpha 2 agonists
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael C Reade, MBBS DPhil
Organizational Affiliation
Austin Hospital & University of Melbourne
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Rinaldo Bellomo, MD
Organizational Affiliation
Austin Hospital and University of Melbourne
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
John Mulder, MBChB
Organizational Affiliation
Western Hospital, Melbourne
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ben Cheung, MBBS
Organizational Affiliation
Toowoomba Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anthony Delaney, MBBS
Organizational Affiliation
Royal North Shore Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Andrew Davis, MBBS
Organizational Affiliation
The Alfred
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Steve Webb, MBBS
Organizational Affiliation
Royal Perth Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael Bailey, MSc PhD
Organizational Affiliation
Monash University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Glenn Eastwood, BNurs RN
Organizational Affiliation
Austin Hospital, Melbourne Australia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Royal North Shore Hospital
City
St Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
Toowoomba Hospital
City
Toowoomba
State/Province
Queensland
ZIP/Postal Code
4350
Country
Australia
Facility Name
Northern Hospital
City
Epping
State/Province
Victoria
ZIP/Postal Code
3076
Country
Australia
Facility Name
The Western Hospital
City
Footscray
State/Province
Victoria
ZIP/Postal Code
3011
Country
Australia
Facility Name
Austin Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
The Alfred Hospital
City
Prahran
State/Province
Victoria
ZIP/Postal Code
3181
Country
Australia
Facility Name
Royal Perth Hospital
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6001
Country
Australia

12. IPD Sharing Statement

Citations:
PubMed Identifier
26975647
Citation
Reade MC, Eastwood GM, Bellomo R, Bailey M, Bersten A, Cheung B, Davies A, Delaney A, Ghosh A, van Haren F, Harley N, Knight D, McGuiness S, Mulder J, O'Donoghue S, Simpson N, Young P; DahLIA Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group. Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients With Agitated Delirium: A Randomized Clinical Trial. JAMA. 2016 Apr 12;315(14):1460-8. doi: 10.1001/jama.2016.2707. Erratum In: JAMA. 2016 Aug 16;316(7):775.
Results Reference
derived

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Dexmedetomidine to Lessen Intensive Care Unit (ICU) Agitation

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